Enteric gelatin capsule shell or envelope



Patented Dec. Q, 1945 ENTERIC GELATIN CAPSULE SHELL OR ENVELOPE SereckH. Fox, Birmingham, and Laurens Paterson Opferman, Detroit, Mich.,assignors to Gelatin Products Corporation, Detroit, Mich., a corporationoi Michigan No Drawing. Application September 24, 1942, Serial No.459,598

4 Claims.

This invention relates to an improved gelatin envelope or protectiveenclosure for medlcaments or other substance which envelope or enclosureis enteric.

This improvement is herein described as particularly relating to anenteric capsule shell but it may be embodied in an envelope or enclosuresurrounding a tablet or medicament in any suitable dosage form.

Heretofore, medicaments intended for intestinal dispersion and havingindividual dosages in tablet. pill, or capsule form have been coatedwith various types oi enterlc coatings. Gelatin is the commonly usedcapsule shell material and gelatin capsule shells have been so coatedbut so far as is known there has not been available a gelatin or othersheet of enteric character which possessed the necessary physicalcharacteristics for use as capsule shell material.

One form of enteric coating usedwas a phthalic acid ester of cellulose.such material was applied as were other enteric coating .materials as acoating to the outer surface the medicamentwhich might be in the form ofa pill or tablet, or applied as a coating to the outer surface of acapsule shell. Such enteric material was alway applied as a coating toan otherwise seli' contained medicament dosage. If the medicament was influid form it was first capsulated as within a gelatin shell and theenteric material was applied as a coating to the capsule shell. Suchcoating materials lacked the elasticity and flexibility of gelatin andwere not suitable for use in sheet form as capsule shells. Such coatingmaterial possessed the disadvantage under certain circumstances ofbreaking down through developgnent of cracks or fissures therein. Theywere particularly unsuitable when used as a coating upon a gelatincapsule shell not only for the above reasons but tor the further reasonthat due to change in size and shape or the capsule shell as a result ofaccidental deformation or temperature variations, the coating filmtended to rupture and break.

This invention is directed toward the provision of an improved gelatinenvelope or sheet material which may be used in the formation of anenvelope 0! capsule shell and which will protect the medicament from theaction of the stomach secretions upon passage or the medicamenttherethrough but which will break down upon exposure to the intestinalsecretions, releasing the medicament therein. We have discovered thatwhen a suitable cellulose derivative, which is water soluble, such asthe sodium salt of cellulose acetate phthalate, is added in relativelysmall percentage such as live to ten per cent to a suitably plasticizedcommercial gelatin solution, and such solution used to form a capsuleshell or envelope for a medicament, and when such capsule shell issubjected to a suitable tanning treatment that the capsule so formedwill pass through the stomach without release of its containedmedicament but will break down in the intestines sufllciently to releasethe medicament. The gelatin solution may be the conventional one ofone-third gelatin, one-third water and one-third glycerin, or it may bea relatively harder gelatin mixture wherein the glycerin content isreduced.

For example, we have found that a suitable gelatin mixture may beprepared as follows:

Grind the cellulose acetate hydrogen phthalate on a micro pulverizer orotherwise suitably pulverize the same. Determine the theoretical amountof sodium acid carbonate required to neutralize and dissolve thecellulose acetate phthalate which commercially varies in degree ofesterlfication. Mix the required amount of sodium bicarbonate with thephthalate as by dry mixing in a Hobart mixer for 10-15 minutes. Add 8lbs. of C. water to the mixture and mix until all phthalate has goneinto solution. Allow to stand overnight to permit complete reaction andevolution of all gas. Add 4 /2 lbs. glycerin to 5 lbs. water; addgelatin with mixing. Allow to soak overnight. Next morning add thephthalate solution to the soaked gelatin with stirring. Break up alllarge aggregates of gelatin. Put in gel tank and melt at 60 C. Maintainon heat until air and CO2 free. Such a gelatin solution should be freefrom undissolved phthalate. The pH should not exceed 7-7.5.

Such a gelatin solution will form a suitable band or sheet capable ofuse in a capsulating machine and may be used to form a, capsule shellenclosing a suitable medicament or to form other enveloping enclosures.

A suitable tanning treatment is to formalize 2 I a,seo,oss

the capsule shell thus prepared in a 1% iormaldehyde solution forforty-rive or sixty seconds tollowedbywashinginwateranddrying.Thetannlng may be accomplished inother suitable ways such as through theemployment of chromic acid of the shell is resistant to attack by thestomach juices whereby the capsule passes through the stomach withoutrelease of its content. When the capsule enters into the intestineshowever. the shell breaks down suiliciently to'release the contentmaterial. It is believed that while the tanned gelatin is stillresistant to solution, be cause of its tanning, that the cellulosederivative traction of the shell responds to the intestinal secretionsand the phthalate reverts to the soluble alkali salt providing openingsthrough the shell which cause it to break down and release its contentmaterial.

It is understood that the water soluble form so oi the cellulosederivative changes to the waterinsolubleiorminthestomachduetotheralatively blah acid environment iolmdthere.

What we claim: 1. A content material surrounded by a tanned gelatinenvelope which has dispersed throughout a sumcient amount of an alkalimetal salt oi cellulose acetate phthalate to render the enveloperesponsive to the action 01 the intestinal secrelO tions to release thecontent substance while re- 'sisting dissolution in the acid stomachsecretions.

2. A medicament surrounded by a tanned gelatin envelope which envelopecontains in dispersed admixture with a selatin 5% to 10% b7 15 webht ofan alkali metal salt of cellulose acetate phthalate.

3. A medicament surrounded by a tanned gelatin envelope which envelopecontains in dispersedadmixturcwiththeselatinasmallper-Y zo centage ofsodium salt of cellulose acetate phthalate in sui'ilcient amount tocause the envelope to release the medicament in response to intestinalsecretions.

4. An enteric capsule shell consisting of a tanas ned gelatin envelopewhich contains in dispersed admixture with a gelatin an alkali metalsalt of cellulose acetate phthalate.

BERECK H. FOX. LAUREN! PA'I'ERBON OFFER-MAN.

